Diabetes Mellitus (“DM”) is a common disease involving ineffective regulation of blood glucose levels. There are over 25 million people in the United States with DM, and recent projections suggest that over 350 million people have the disease worldwide. There are two primary forms of DM. Type I DM generally affects children and young adults and is related to a primary deficiency of the insulin hormone. Type II DM usually affects adults, often over the age of 50, but increasingly in younger adults as well. It is a complex disease that generally starts as a resistance to insulin action that may progress to secondary insulin deficiency. The causes of Type I and Type II DM are not entirely known although genetic, environmental, and lifestyle risk factors have been identified.
Although acutely high or low blood glucose levels are dangerous, the primary sources of DM-associated morbidity and mortality are the long term macrovascular and microvascular complications of the disease. Macrovascular complications refer to cardiovascular events such as myocardial infarction (“heart attack”) and stroke. Microvascular complications refer to pathological damage to the nerves, eyes, and kidneys of people with DM.
The most common microvascular complication of DM is neuropathy, or nerve damage. Diabetic neuropathy affects 60% or more of people with DM. Diabetic neuropathy may include damage to the large myelinated nerve fibers, the small myelinated and unmyelinated nerve fibers, and the autonomic nerves. The most common form of diabetic neuropathy is the large fiber form of the disease which is often termed diabetic peripheral neuropathy (“DPN”). DPN leads to pain and disability, and is the primary trigger for foot ulcers which may result in lower extremity amputations.
Because of the severe consequences of DPN, early detection of this complication of DM, and interventions to prevent or slow down progression of the neuropathy, are of paramount importance. Unfortunately, detection of DPN is challenging, particularly at its early stages when it may be most susceptible to intervention. Current methods of detecting and monitoring DPN range from clinical evaluation (including symptoms and signs obtained on simple physical examination) to various tests that include the 5.07/10-g monofilament test (where a column of “fishing line” is pressed into the foot of the patient, with the goal being for the patient to detect the contact before the column of “fishing line” bends), the tuning fork test (where a vibrating tuning fork is placed against the big toe of the patient, with the goal being for the patient to detect the vibration of the tuning fork), and quantitative vibration perception testing (where electronics are used to measure the magnitude of a vibration detectable by the patient). While all of these methods have utility, they are subjective, have inadequate sensitivity or specificity, or both, and have poor reproducibility. The “gold standard” method for evaluation of DPN is a nerve conduction study. In a nerve conduction study, a nerve is electrically stimulated at a first location along the nerve, and then the electrical response of the nerve is detected at a second location along the nerve. Among other things, the rate at which the nerve conducts the signal (“the nerve conduction velocity”) and the magnitude of the evoked signal (“the amplitude”) are reliable indicators of neuropathy. Unlike the aforementioned techniques, nerve conduction testing is objective, sensitive, specific, and reproducible. As a result, most clinical guidelines suggest confirmation of DPN by nerve conduction testing for a reliable diagnosis.
Despite its technical and clinical attributes, nerve conduction testing is not currently widely used in the detection and monitoring of DPN. The reasons for this include the limited availability, complexity and high cost of the study when performed by specialists, usually a neurologist, using traditional electrodiagnostic equipment. To overcome these obstacles to adoption, a number of devices have been developed to simplify and increase access to nerve conduction studies through automation and other techniques. For example, devices that perform nerve conduction measurements using pre-fabricated, nerve-specific electrode arrays have been developed that largely automate the required technical steps of a nerve conduction study (see, for example, U.S. Pat. No. 5,851,191 issued to Gozani et al. and U.S. Pat. No. 7,917,201 issued to Gozani et al.). Another related solution found in the prior art (see U.S. Pat. No. 5,215,100 issued to Spitz et al.) is an apparatus for the assessment of Carpal Tunnel Syndrome (CTS) in which all the electrodes required to stimulate and record from the nerve are fixed by the device.
These prior art solutions suffer from a number of deficiencies. All devices described in the prior art are either general purpose (i.e., multi-nerve, multi-application) nerve conduction testing devices or they are designed specifically for evaluation of the median nerve for the assessment of CTS. General purpose devices, of necessity, must adapt to the various anatomical and electrophysiological aspects of many different nerves. As a result, only limited customization is possible and the onus remains on the user of the general purpose device to address the sources of variations—such as through the placement of individual electrodes or even pre-configured electrode arrays. As a result, despite simplifying nerve conduction measurements relative to the traditional approaches, the general purpose testing devices still require a fair amount of training in order to properly perform the nerve conduction test procedures. Also, those devices in the prior art specifically designed for the evaluation of the median nerve have little relevance to the requirements of the present invention, which is the assessment of the sural nerve. The primary reason for this is that the anatomy and electrophysiology of the sural nerve (used for the assessment of DPN) is substantially different from that of the median nerve (used for the assessment of CTS). Therefore devices specifically designed for testing of the median nerve cannot be used to test the sural nerve. Another issue with general purpose testing devices is that they require two discrete components—a device with the electronic circuits needed to perform a nerve conduction test, and a nerve-specific electrode array which provides an interface between the unique characteristics of the particular nerve being tested and the common testing device. This two-component requirement limits attempts to reduce test costs, particularly because it restricts the ability to reduce the size of the electrode array, which is a primary cost driver in nerve conduction testing.